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Dealing With Fatigue

Spring 2007

By itself, fatigue is not a "disease." When persistent and severe, however, fatigue (feeling tired all the time, lacking stamina, having too little energy to do things) can disrupt one's life, interfering with daily activities, socializing, or fulfillment of goals such as returning to work, enrolling in school, or improving life circumstances in other ways.

There is no standard definition or standard measure of fatigue. Being tired all the time may include both psychological components (such as depression) and physical components (climbing stairs tires you out). It is different from apathy, which is loss of desire to do anything, and from oversleeping, which is defined simply as increased sleep time. Common words to describe fatigue include lack of energy, sleepiness, tiredness, exhaustion, an inability to get enough rest in the absence of night-time insomnia, or inability to sustain a desired activity.

Everyone experiences fatigue at some point. It becomes a problem that warrants treatment when it occurs frequently, for sustained periods, and interferes with daily activities. Fatigue occurs in relation to multiple AIDS-associated conditions and also medications, but may also exist without apparent explanation.


Fatigue and HIV

Research studies from our group and others have shown that fatigue is a common and significant problem for a substantial number of people with HIV, and may be due to the virus, to HIV-related medications, or associated health problems or treatments. In various surveys, up to 40% of HIV+ respondents report fatigue, although it is not always persistent or disabling.

When it does persist, fatigue can interfere with many activities Physical activities such as exercise are often reduced, as are social activities, contributing to social isolation and fewer opportunities for pleasant events. People with fatigue may not have the energy to visit friends, or may cancel planned activities because they're too tired to go out.

Fatigue is a common reason for leaving work and going on disability, as well as inability or reluctance to return to work even when one's health is otherwise stable.

Together with other problems, fatigue may interfere with medication adherence, including doses missed for reasons such as falling asleep prematurely or sleeping through a scheduled dose. Fatigue also can interfere with concentration, memory, and the ability to sustain attention, which in turn may interfere with new learning. Overall, persistent fatigue in HIV is common and can be disabling.

Medical Causes

Fatigue may be caused by specific medical conditions, including untreated insomnia, anemia, low levels of testosterone, or thyroid deficiencies. It makes sense to identify and treat these conditions directly before treating the symptom of fatigue. Routine bloodwork can be done to check whether such problems do exist.

Fatigue also may be the result of the drugs used to treat HIV or other conditions. Some psychotropic drugs (Remeron, for example) can cause fatigue. Hepatitis C itself often causes fatigue, and fatigue is one of the major and frequent adverse reactions to alpha interferon/ribavirin treatment of hepatitis. Some studies have shown a relationship between fatigue, higher HIV viral load and lower CD4 cell count, while others have not shown such a relationship.

Fatigue and Depression

People who are depressed often complain about low energy, lack of stamina, or feeling tired all the time. In fact, fatigue is one of the symptoms used to diagnose depression. In addition, fatigue is also associated with problems concentrating and focusing, which is another criterion used to identify depression. There may be the opposite connection as well: when fatigue restricts participation in pleasant events, reduces social activities and leads to long days alone at home, depressed mood is a likely result.

However, since both depression and fatigue are fairly common in people with HIV, they may overlap even if one doesn't cause the other. Each can and does occur without the other. Some people say they always feel tired, but are not persistently depressed. Some patients with depression do not report fatigue. So the two conditions may occur together or separately. If both are present, and the depression is moderate or severe, it is best to treat the depression first, on the principal that it is preferable to treat the cause of a problem rather than its manifestation. If fatigue remains, then it can be treated subsequently.

Treating Fatigue

Several treatment approaches have been used to treat fatigue in the context of HIV infection. One approach is to use steroid hormones such as testosterone or DHEA. Studies, including those from our group, have shown that, among men, testosterone injections have a clearcut positive effect on energy level and stamina. Injected testosterone is no longer commonly recommended, however, given the availability and greater convenience of gel preparations. Testosterone gel has not been systematically evaluated with respect to effects on fatigue in HIV+ men, although we often see patients seeking treatment for fatigue who have already tried gel testosterone preparations without effects on their fatigue. Furthermore, testosterone is not appropriate for men with prostate problems or men with bipolar disorder (extreme mood swings), and is not approved for use by women.

The results for DHEA are less consistent; some patients have found it helpful for fatigue but others have not, in research we have conducted. However, DHEA has few side effects, is sold over the counter without the need for a prescription (which means that health insurance does not cover the cost although it is inexpensive), and at higher doses than often sold can be helpful, at least for some people, for mildly depressed mood as well as low energy. DHEA increases testosterone level in women but not in men.

The other main class of medications used to treat fatigue in HIV+ people includes stimulants such as Dexedrine, Ritalin, and Cylert. In one study comparing Ritalin, Cylert, and placebo, both drugs were more effective than placebo -- but overall, most study participants did not show significant improvement to any of them.

In the early 1990s (before HIV combination therapy was available) our group conducted a small study of Dexedrine in people with CD4 counts below 50, and found a major positive effect on energy as well as mood. However, most health providers are reluctant to prescribe these controlled substances because of concerns about physiological as well as psychological dependence, and they are generally not appropriate for patients with addiction histories. Stimulants as well as steroids also are not indicated for those with bipolar disorder (manic depression) since they may cause the onset of manic episodes.

In the past few years, a new stimulant medication has been marketed, known as Provigil. It isn't fully understood how it works in the brain, but it is different from other stimulants and shows no evidence of potential for addiction. In fact, it has been used with some preliminary evidence of success for treatment of cocaine addiction. Provigil is approved for the treatment of narcolepsy (a condition where one falls asleep suddenly and involuntarily during the day), sleep apnea, or shift work-related sleep disorder. Its use to treat fatigue in HIV is thus "off label," which is why research is needed concerning its effectiveness for HIV+ people with fatigue.

We conducted a preliminary study with 30 HIV+ men and women with persistent fatigue who were taking HIV medications. In this exploratory study, most participants found Provigil helpful, although the results are at best suggestive, since this was a small study and both doctors and patients knew they were taking Provigil. Side effects were uncommon, but when they occurred included feeling jumpy, "wired," or having a headache -- not unlike drinking too much coffee. These side effects were gone the next day, and could be managed by lowering the dose. No patients discontinued the medication because of side effects. We monitored CD4 counts and viral load, and found no changes, providing some evidence that there are no harmful interactions with HIV medications. By the end of this 12-week trial, five patients started working again, two others increased their hours of work, and two enrolled in vocational training programs.

We are now conducting a larger placebo-controlled trial in people with HIV who have persistent fatigue that interferes with their everyday life. We hope to learn more about rates of response, who seems most likely to benefit from this treatment, how long the effects last, and whether it is helpful for problems with memory and attention. We also are conducting studies to make sure that Provigil is safe and effective in combination with HIV medications.

In conclusion, fatigue can be "real" and can represent a significant problem. It isn't just being lazy or not trying hard enough, especially if you are often too tired to do things and go places. Treatment can help, options are available, and quality of life can improve.

Judith Rabkin is a clinical psychology researcher at Columbia University.

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This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.
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